IMAGE: Dr. William 'Bill' Grady is a member of the Clinical Research Division at Fred Hutch.
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Credit: Photo by Scott Streble for Fred Hutch

Dr. William Grady, a clinical researcher and cancer geneticist at Fred Hutch, has been awarded a $180,000 grant from the DeGregorio Family Foundation for Gastric and Esophageal Cancer Research and the Price Family Foundation for a two-year project to develop a better way to identify people at highest risk for esophageal adenocarcinoma, the most common cancer of the esophagus.

Incidence of esophageal cancer is rapidly increasing in the United States. Last year, roughly 20,000 Americans died of it, which is more than a fivefold increase compared to the early 1970s.

The risk of adenocarcinoma increases with age, obesity and tobacco use. However, it is tenfold higher for individuals with Barrett's esophagus, a change in the esophageal lining that occurs in people who have chronic heartburn and gastroesophageal reflux. Cancer in patients with Barrett's esophagus can be prevented or treated successfully if caught early by endoscopy, a medical exam that allows doctors to look at the lining of the esophagus.

Endoscopies, unfortunately, are unpleasant and intrusive, and because just a fraction of those with Barrett's esophagus ever develop cancer, most people with the condition likely do not need them. The problem is that doctors have no way to tell which patients with Barrett's esophagus are at the highest risk for cancer. Grady's team aims to find a simple way to spot those patients who should get frequent endoscopies, while sparing others unnecessary discomfort.

He and research partner Dr. Georg Luebeck, a computational biologist and member of the Public Health Sciences Division at Fred Hutch, plan to achieve this with a test that can accurately determine the biological age of esophageal tissue, which results from biochemical wear and tear ? and differs from chronological age, as told by the calendar. Their focus is on detecting a process of chemical build-up on DNA, called DNA methylation, which Grady likens to rust. More "rust" means faster biological aging and presumably a higher risk of cancer.

With the funding from this new grant, Grady and Luebeck will compare the "rust" profiles in tissue samples of Barrett's esophagus patients who developed esophageal cancer with those who did not. Their goal is to use any differences between the profiles as the basis of a screening test that can tell Barrett's esophagus patients in the future whether they should start getting endoscopies and how often they should get them.

"The biological age of the esophagus will allow us to determine the true cancer risk for someone with Barrett's esophagus," said Grady, who is a member of Fred Hutch's Clinical Research Division and a practicing physician at Seattle Cancer Care Alliance. "We think a person with an older esophagus will have a higher cancer risk than a person with a young esophagus."

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The DeGregorio Family Foundation raises funds to financially support critical research grants to facilitate early detection and effective treatment therapies for the deadly diseases of stomach and esophageal cancer.

Lynn DeGregorio, founder and president of the foundation, said of the award, "This year was our most competitive application process yet. The DeGregorio Family Foundation, along with a major contribution by the Price Family Foundation, are happy to support Dr. Grady's research. We believe the science proposed is novel and innovative and will feasibly lead to a better understanding of esophageal cancer."

At Fred Hutchinson Cancer Research Center, home to three Nobel laureates, interdisciplinary teams of world-renowned scientists seek new and innovative ways to prevent, diagnose and treat cancer, HIV/AIDS and other life-threatening diseases. Fred Hutch's pioneering work in bone marrow transplantation led to the development of immunotherapy, which harnesses the power of the immune system to treat cancer with minimal side effects. An independent, nonprofit research institute based in Seattle, Fred Hutch houses the nation's first and largest cancer prevention research program, as well as the clinical coordinating center of the Women's Health Initiative and the international headquarters of the HIV Vaccine Trials Network. Private contributions are essential for enabling Fred Hutch scientists to explore novel research opportunities that lead to important medical breakthroughs. For more information visit http://www.fredhutch.org or follow Fred Hutch on Facebook, Twitter or YouTube.

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